1. The Assessment Of Sequential Antibiotics Therapy In University Malaya Medical Centre (UMMC) Che Zuraini Sulaiman Pharmacist UMMC

2. INTRODUCTION Sequential Antibiotics Therapy the conversion of intravenous to oral antibiotic treatment using the same medication (Lelekis, et al. 2001) Pre-set criteria to direct sequential antibiotic therapy vs physician-directed conversion Advantages Cheaper treatment costs (Lelekis, et al. 2001) Shortens LOS (Lelekis et al., 2001, Hunter et al., 1995, van der Eerden et al., 2004) Reduce IV catheter-related complications ( (Lelekis, et al. 2001, van der Eerden et al., 2004, Vogel, F, 1995) Convenient to patients and hospital personnel (Vogel, F, 1995)

3. AIM & OBJECTIVES AIM  To assess the need to establish a sequential antibiotic therapy program in UMMC OBJECTIVES 1.To identify the current practice of IV-to- oral conversions in UMMC 2.To calculate the potential cost-savings of sequential antibiotic therapy

4. METHODOLOGY

5. STUDY DESIGN prospective observational study DURATION OF STUDY Dec 2006 - Feb 2007 STUDY POPULATION all patients admitted to UMMC receiving targeted antibiotics and fulfilling the inclusion criteria CALCULATED SAMPLE SIZE 302 (confidence level 95%, confidence interval 5%, estimated prevalence 0.50)

6. Targeted Antibiotics Ampicillin Azithromycin Benzypenicillin Clindamycin Cloxacillin Cotrimoxazole Amoxicilin/clavulanic acid Ciprofloxacin Ampicillin/sulbactam Cefuroxime

7. Inclusions -soft tissue infection -RTI -UTI -blood infection -intra-abdominal infection Exclusions  Malignancy  Neutropenia or immuno- compromised  Concomitant infections requiring IV antibacterials for sustained periods  Pregnant or moribund  Concomitant disease states that contraindicate the use of oral medications

9. CRITERIA FOR IV TO ORAL CONVERSION (based on Dundee Infectious Disease Unit Criteria for Intravenous-Oral Switch & Duke University Medical Centre Criteria for Switching to Oral Antimicrobial Therapy) -Signs and/or symptoms of infection are improved or have resolved according to physician’s assessments -Patient is afebrile (Temperature ≤37.9°C) or has had consistent improvement in fever over a 24-hour period -White blood cells are normalizing (if repeated measurements are available) -GI absorption of drugs is normal (absence of vomiting or abnormal GI anatomy) -The patient is able to receive enteral therapy (orally or through gastric feeding tubes) as evidenced by concomitant enteral medications or nutrition -No evidence of continuing sepsis with two or more of the following: temperature >38˚C, pulse >90 beats/min, respiratory rate >20 breaths/min or white cell count 12x10 9 /L

10. 1)Percentage receiving sequential antibiotic therapy 2)Outcome of sequential antibiotic therapy 3)Potential cost savings of sequential antibiotic therapy potential cost saving of sequential antibiotic therapy = antibiotic acquisition cost for IV antibiotic _ antibiotic acquisition cost for oral antibiotic

15. 385 patients’ case notes reviewed 212 patients included 196 patients met criteria for IV to oral conversion (92.5%) 16 patients did not meet criteria for IV to oral conversion (7.5%) Converted to oral antibiotics (n=172) Not converted to oral antibiotics (n=24) Potential cost saving: RM1794.30 Converted before criteria were met (n=35) Clinical cured: n=35 (100%) Converted when criteria were met (n=38) Clinical cured: n=38 (100%) Converted after criteria were met (delayed conversion) (n=99) Clinical cured: n=99 (100%) Potential cost saving: RM13948.70

16. MEAN (±SD) DURATION CRITERIA FOR IV TO ORAL CONVERSION WERE MET (N=196 ) Criteria for IV to oral conversion, N=196 Mean (±SD) duration to meet criteria, day(s) Criterion 1 Signs and/or symptoms of infection are improved or have resolved according to physician’s assessments 3.9 (±2.3) Criterion 2 Patient is afebrile (Temperature ≤37.9°C) or has had consistent improvement in fever over a 24-hour period 2.3 (±1.9) Criterion 3 White blood cells are normalizing (if repeated measurements are available) 2.4 (±2.2) Criterion 4 GI absorption of drugs is normal (absence of vomiting or abnormal GI anatomy) 1.2 (±1.0) Criterion 5 The patient is able to receive enteral therapy (orally or through gastric feeding tubes) as evidenced by concomitant enteral medications or nutrition 1.4 (±1.3) Criterion 6 No evidence of continuing sepsis (with two or more of the following: temperature  38˚C, pulse  90 beats/minute, respiratory rate  20 breaths/minute or white cell count  4 or  12x10 9 /L) 1.1 (±0.6) All criteria4.3 (±3.3)

17. 385 patients’ case notes reviewed 212 patients included 196 patients met criteria for IV to oral conversion 16 patients did not meet criteria for IV to oral conversion Not converted to oral antibiotics (Group 4) (n=24) (12.2%) Potential cost saving: RM1794.30 Delayed conversion (Group 3) (n=99) (50.5%) Clinical cured: n=99 (100%) Potential cost saving: RM13948.70 Converted when criteria were met (Group 2) (n=38) (19.4%) Clinical cured: n=38 (100%) Converted before criteria were met (Group 1) (n=35) (17.9%) Clinical cured: n=35 (100%) Converted to oral antibiotics (n=172) (87.8%)

18. IV TO ORAL CONVERSION OF ANTIBIOTICS ACCORDING TO SITES OF INFECTION (N=196)

19. 385 patients’ case notes reviewed 212 patients included 196 patients met criteria for IV to oral conversion 16 patients did not meet criteria for IV to oral conversion Converted when criteria were met (Group 2) (n=38) Clinical cured: n=38 (100%) Converted before criteria were met (Group 1) (n=35) Clinical cured: n=35 (100%) Converted to oral antibiotics (n=172) Not converted to oral antibiotics (Group 4) (n=24) Potential cost saving: RM1794.30 Delayed conversion (Group 3) (n=99) Clinical cured: n=99 (100%) Potential cost saving: RM13948.70

20. OUTCOME OF TREATMENT (All patients receiving sequential antibiotic therapy)  Clinical cure (100%) TOTAL POTENTIAL COST SAVING (in 123 patients in 2 months)  RM15743.00 Potential cost saving per patient Potential annual cost savings :::: RM127.99 RM94458.00

21. STUDY LIMITATIONS  exclusion of patients receiving targeted antibiotics that were kept as ward stock  inability to perform a detailed cost analysis

22.  sequential antibiotic therapy is commonly practised in UMMC  the conversions from IV to oral antibiotics are often delayed  total potential cost savings was estimated to be approximately RM100,000 annually

23. RECOMMENDATIONS  Establishment of a safe and cost- effective policy of sequential antibiotic therapy in UMMC  Development of a set of criteria for IV to oral conversion with the help of ID team  Implementation of sequential antibiotic therapy program through team approach

24. Acknowledgement Ms Ho See Wan 1, Ms Reena Rajasuriar 1, Prof Dr Adeeba A Kamarulzaman 2 1 Department of Pharmacy, University Malaya 2 Infectious Disease Unit, University Malaya Medical Centre

26. 1. Lelekis, M & Gould, IM 2001, ‘Sequential antibiotic therapy for cost containment in the hospital setting: why not?’, Journal of Hospital Infection, vol. 48, no. 4, pp. 249-257. Retrieved July 25, 2006, from Science Direct database. 2. Shah, PM 2000, ‘Sequential or switch treatment - which criteria should be fulfilled?’, International Journal of Antimicrobial Agents, vol. 16, no. 301, pp. 301-302. Retrieved July 25, 2006, from Science Direct database. 3. Hunter, KA & Dormaier, GK 1995, ‘Pharmacist- managed intravenous to oral step-down program’, Clinical Therapeutics, vol. 17, no. 3, pp. 534-540. Retrieved July 16 2006, from Science Direct database.

27. 4. van der Eerden, MM, de Graaff, CS, Vlaspolder, C, Bronsveld, V, Jansen, HM & Boersma, WG 2004, ‘Evaluation of an algorithm for switching from IV to PO therapy in clinical practice in patients with community-acquired pneumonia’, Clinical Therapies, vol. 26, no.2,pp. 294-303. 5. Vogel, F 1995, ‘Sequential therapy in the hospital management of lower respiratory infections’, The American Journal of Medicine, vol. 99, no. supplement 6B, pp. 14S-19S. 6.Barlow, GD & Nathwani, D 2000, ‘Sequential antibiotic therapy’, Current Opinion in Infectious Diseases, vol. 13, no. 6, pp. 599-607.

28. Thank You

29. Formula number of days of delayed conversion=number of days with IV antibiotic−day all criteria of conversion were met acquisition cost for IV antibiotic=number of days of delayed conversionxbasic units of IV antibiotic given per dayxbasic unit acquisition price of IV antibiotic acquisition cost for oral antibiotic=number of days of delayed conversionxbasic units of oral antibiotic given per dayxbasic unit acquisition price of oral antibiotic the potential cost saving of antibiotic acquisition cost=antibiotic acquisition cost for IV antibiotic−antibiotic acquisition cost for oral antibiotic